Xanthine oxidase is an enzyme catalyzing the conversion of hypoxanthine to xanthine and further to uric acid in nucleic acid metabolism.
A xanthine oxidase inhibitor inhibits uric acid synthesis to reduce a level of uric acid in the blood with respect to the action of xanthine oxidase. Thus, a xanthine oxidase inhibitor is effective as a therapeutic agent for hyperuricemia and various diseases caused by hyperuricemia. Moreover, there are gouty arthritis and gouty tophus called gout as a clinical condition caused by as a result of deposition of urate crystals after prolonged hyperuricemia. In addition, hyperuricemia is considered to be important as a factor of lifestyle diseases associated with obesity, hypertension, dyslipidemia and diabetes or metabolic syndromes, and recently, it has been clarified that hyperuricemia is a risk factor of renal damage, urinary calculi and cardiovascular diseases by epidemiological studies (guideline for the Management of Hyperuricemia and Gout, 2nd edition). In addition, a xanthine oxidase inhibitor is expected to be useful for a treatment of diseases related to reactive oxygen species by its inhibitory activity on reactive oxygen species generation, for example, a treatment of cardiovascular diseases through improvement of endothelial function (Circulation. 2006; 114:2508-2516).
Allopurinol and febuxostat are clinically used as a therapeutic agent for hyperuricemia, but allopurinol has been reported to have a side effect such as Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic disorder and renal dysfunction (Nippon Rinsho, 2003; 61, Suppl. 1: 197-201).
As a compound having a xanthine oxidase inhibitory activity, for example, a 2-phenylthiazole derivative is reported (Patent Documents 1 to 3).
On the other hand, in Patent Documents 4 and 5, a dithiazole carboxylic acid derivative having a benzene ring in the center is reported. Further, in Patent Documents 6 and 7, a biphenyl thioazole carboxylic acid derivative is reported.